Anal cancer risk and HPV infection knowledge and awareness among Hispanic persons living with HIV in Puerto Rico

Background: Persons living with HIV (PLWH) have a higher risk of persistent infection with human papillomavirus (HPV) and anal cancer. We evaluated knowledge and awareness of HPV infection and risk factors for anal cancer among PLWH in Puerto Rico (PR). Methods: Data from a cross-sectional study (2020–2021) were analyzed (n=212). Inclusion criteria included PLWH, aged ≥ 26 years, and living in PR. Telephone interviews collected information on sociodemographic, lifestyle and clinical characteristics. Two 13-item scales were used to assess knowledge of HPV and anal cancer risk factors; adequate knowledge for both scales were defined as scoring >70%. Logistic regression models using generalized linear models were used to determine the association between 1) HPV infection awareness, 2) HPV infection knowledge, and 3) Anal cancer risk factors knowledge. Results: The median age was 54 years (IQR: 46,58), 67.5% were male, 71.7% reported having an income <$20,000, and 54.3% had an education level of more than high school. HPV awareness was high (82.1%), but only 40.2% and 3.8% had adequate knowledge of HPV and anal cancer risk factors, respectively. In adjusted logistic regression models, men who have sex with men (OR: 1.26, 95%CI: 1.07–1.47) and women (OR: 1.35, 95%CI: 1.15–1.59) aged ≥50 years had higher odds of HPV awareness than heterosexual men in that age group. Moreover, those with history of anal Pap test aged <50 years had more HPV awareness (OR 1.34, 95%CI: 1.08–1.66) than their counterparts. Adequate HPV knowledge was higher among participants with an education level of more than high-school (OR:1.28, 95%CI: 1.10–1.50) and with a history of HPV diagnosis (OR:1.33, 95%CI: 1.08–1.65) than their counterparts. In addition, people with good/very good/excellent health perception had higher odds of HPV knowledge (OR:1.23, 95%CI: 1.03–1.47) than those who reported poor/regular health perception. For anal cancer risk factors, PLWH for ≥15 years had increased odds of having adequate knowledge (OR:1.07, 95%CI: 1.02–1.14) than their counterparts. Conclusions: Despite high awareness of HPV, limited knowledge about HPV and anal cancer risk factors was observed among PLWH. Results from our study highlight the need for educational efforts within this population as an anal cancer prevention strategy.


BACKGROUND
People living with human immunode ciency virus (PLWH) have a higher risk of persistent infection with human papillomavirus (HPV) and consequently anal cancer (AC).HPV infection is the principal riskfactor for AC.(1) The occurrence of this uncommon cancer is gradually increasing.In Puerto Rico (PR), the incidence rate of AC was higher among PLWH than in the general population (27.7 versus 1.1 per 100,000 person-years) from 2000 to 2016.(2) This is also higher compared to the United States (US) national incidence, 1.9 per 100,000 person-year.(3) AC incidence is associated with HPV risk-factors, such as sexual behaviors, including anal intercourse and multiple sexual partners.Additionally, PLWH, men who have sex with men (MSM), women with HPVrelated cervical cancer or precancerous lesions, and immunosuppressed individuals (due to organ transplants or autoimmune disorders) are at high-risk.(4)Furthermore, older age, female sex and smoking are other factors associated with AC. (4) High-risk individuals must have early diagnosis and screening for AC.(5) At early stages, AC could be asymptomatic or present with symptoms like other non-serious conditions.These may include anal bleeding, anal or pelvic pain, weight loss, sensation of a mass in the anus or rectum, anal irritation, tissue prolapse, atus or stool incontinence, and obstipation.(6)The anal Papanicolaou (Pap) test is the principal screening approach recommended for PLWH.This clinical practice was not supported by clinical guidelines (7) until February 2024, when the consensus guidelines of the International Anal Neoplasia Society (IANS) for the screening of AC were published.(5) Integrating this approach proposes an important intervention to reduce the risk of AC among high-risk populations.
(5) Although AC screening is recommended for PLWH; research suggests that lack of knowledge and awareness about HPV infection and AC risk-factors could in uence the uptake of AC screening.(8)(9)(10) Therefore, this study aimed to assess awareness and knowledge of HPV infection, AC risk-factors, and perceived risk among PLWH in PR.

Study design and population.
Data from a cross-sectional study conducted from November 2020 to December 2021 was analyzed.Participants had to be: 1) PLWH, 2) aged 26 years and older, and 3) living in PR.Potential participants were identi ed through social media, on-site clinic promotion with research assistants, yers/banners at immunologic clinics, TV and radio advertising, and participants' word of mouth.Of the 370 possible candidates contacted, 290 were interested in participating, 268 were eligible, and 212 (79%) PLWH participated in the study.Individuals who consented completed a telephone interview where information about sociodemographic, lifestyle, and clinical characteristics was gathered.This study was approved by the Institutional Review Board of the University of Puerto Rico Comprehensive Cancer Center (2019-07-10).

Data collection.
HPV awareness was dichotomized (Yes/No).The "Yes" category included participants who answered "yes" to the question "Before today, have you ever heard of HPV infection?"; the "No" categoryincluded those who answered "no" or "do not know".
To evaluate HPV and AC knowledge, two 13-item scales were constructed.The HPV infection knowledge scale included questions regarding risk-factors for HPV infection, and HPV-associated cancers, among others.The AC risk-factors knowledge scale included questions regarding HIV, tobacco use, HPV infection, and anal sex (See table 3).( 11) All questions could be answered as: "Yes", "No", "Do not know", and "Refuse to answer".These answers were then coded as correct or incorrect (Don't know answers were classi ed as incorrect).For both scales, responses were summed and divided by the number of questions (n=13).Participants who scored ≥70% were classi ed as having adequate knowledge whereas those who scored <70% were classi ed as not having adequate knowledge.

Statistical analysis
Frequencies were used to describe categorical variables, whereas central tendency measures were used for continuous variables.Chi-square statistics and Fisher exact test were used to assess the association between HPV infection knowledge and AC risk-factors and the other covariates.Logistic regression models using generalized linear models were used to determine the association between HPV infection awareness, HPV infection knowledge, and AC risk-factors knowledge, and the potential predictors that were statistically signi cant in the bivariate analysis (p<0.05).The Likelihood Ratio test assessed the interaction terms between the predictor variables.If an interaction term had a p-value of less than 0.05, the model was strati ed by this variable.When no interaction terms were seen, the models were adjusted according to sexual risk group and age.Stata for Windows, version 17 (Stata Corporation, College Station, TX) was used for the statistical analysis.

RESULTS
The median age of the participants was 54 years (IQR: 46, 58).The majority (67.5%) reported being assigned male sex at birth, having an income less than $20,000 (71.7%), an education level of high school or more (54.3%),and having government health insurance (84.4%).Furthermore, 44% of the participants were MSM, 33% were women and 23% were men who have sex with women (MSW).The median years for living with HIV was 17 years (IQR: 9-25).Almost all participants reported using antiretroviral therapy (99.1%), and 20.8% reported having a history of acquired immunode ciency syndrome (AIDS).
The self-reported prevalence of HPV infection was 12.0%.Although awareness of HPV vaccination was 53.8%,only 7.6% of the participants reported being vaccinated against HPV infection.More than half of the participants reported a history of sexually transmitted infections (STIs) (63%), while none reported having a history of AC.Regarding lifestyle characteristics, 29.3% reported being current smokers, 55.2% reported current alcohol intake and 64.1% reported use of non-IV drugs in their lifetime.Furthermore, more than half (80.2%) perceived having excellent/very good or good health.(Table 1) HPV awareness was high among the study population (82.1%), but only 40.2% had adequate HPV knowledge (score ≥70).The majority correctly answered items about the risk of acquiring HPV; HPV can be transmitted by sexual contact (89.1%), having sex with multiple partners (95.4%), partners with multiple sexual partners (91.4%), or having sex at early ages (71.8%).When asked about HPV-related cancers, most of the participants correctly identi ed cervical cancer (87.4%),AC (83.9%) and oral cancer (67.2%).More than half think that HPV is uncommon (66.1%), that HPV-infected people always present symptoms (66.1%), and that genital warts are caused by HPV (62.6%).On the contrary, less than half think that condoms always prevent HPV infection (43.7%), and that HPV can disappear without treatment (8.6%).
Regarding AC, only 3.8% of the study population had adequate knowledge of AC risk-factors.However, a high proportion of participants correctly identi ed number of sex partners (87.3%),HPV infection (81.6%), unprotected sex (78.3%), anal sex (76.4%),HIV (69.8%), smoking (66.5%), and having gynecologic cancers (62.4%) as risk-factors for AC.Most felt they were at higher risk of AC than other people of the same age (51.4%).Some of the participants thought that screenings for AC are uncomfortable (40.0%), most of them had anal Pap (52.2%) history and the majority (59.6%) had done the anal Pap in the last 12 months.Additionally, 76.9% have considered getting tested for AC, and 96.7% indicated they will do the anal Pap test in the future (Data not shown).However, a history of highresolution anoscopy (HRA) uptake was less common (19%) in this population.

Bivariate analysis
HPV awareness was signi cantly higher among women (89.9%), people with a history of anal Pap uptake (89.0%), and men who have sex with men (83.9%) (p<0.05).No other signi cant differences were seen.
(Table 2) Higher HPV knowledge adequacy was observed in participants with an education level of more than high school (51.6% vs 26.0%) and with a history of HPV infection (65.2% vs 35.8%).Also, participants with a history of sexually transmitted infections (47.8% vs 26.2%) and with a self-reported health perception of excellent/very good or good (45.6% vs 21.1%) showed more knowledge about HPV infection (p<0.05).
(Table 4) An association was seen between having adequate knowledge of AC risk-factors and the years living with HIV.More speci cally, 6.8% of individuals living with HIV for 15 years or more had adequate knowledge of AC as compared to 0.0% of those who had lived with HIV for less time (p<0.05).(Table 4)

Multivariate analysis
Given signi cant interactions with age, logistic regression models were strati ed by age-group (Table 5).
In multivariate logistic regression models, participants with an education level of more than high school (OR: 1.28, 95% CI: 1.10-1.50)and with a history of HPV diagnosis (OR: 1.33, 95%CI: 1.08-1.65)were more likely to have adequate HPV knowledge compared to their counterparts.In addition, PLWH who reported having good/very good/excellent health were more likely to have adequate knowledge as compared to those who reported poor/regular health (OR: 1.23, 95% CI: 1.03-1.47).Although not statistically signi cant, participants with a history of STIs (OR: 1.13, 95% CI: 0.97-1.32)were also more likely to have adequate HPV knowledge.(Table 6) For knowledge of AC risk-factors, PLWH for 15 years or more had increased odds of having adequate knowledge (OR: 1.08, 95% CI: 1.02-1.14)compared to those diagnosed more recently (data not shown).

DISCUSSION
Awareness and education play a pivotal role in adopting healthy behaviors and facilitating opportune detection and management of acute conditions like AC. (12,13) Therefore, cancer control and prompt detection are directly related to risk-factors awareness, knowledge, and improved likelihood of survival (14,15).Thus, populations at increased risk of developing cancer must be aware of risk-factors to adopt protective behaviors.It is known that PLWH has a major risk to have HPV infection and in consequence AC, hence awareness and education about HPV and AC risk-factors are imperative among this population.
The principal aim of this study was to assess awareness and knowledge of HPV infection and AC riskfactors among PLWH in PR.The results showed that although PLWH were aware of HPV, their knowledge about this condition was limited.Likewise, results are consistent with studies completed by Feeney, et al.
(8) and Adegboyega et al.( 16), where poor knowledge and awareness of HPV were described in HIVpositive and negative gay and bisexual men and African Americans and African immigrants' young adults, respectively.Nevertheless, according to results from our study in PLWH living in PR, education, previous history of HPV infection and STIs seem to positively in uence HPV infection and AC knowledge, similar to other studies where a higher education (17)(18)(19) is related to higher knowledge about HPV infection and AC.Similarly, another study among high-risk men of Hispanic living in PR showed that a history of STIs was associated with a higher knowledge of HPV infection.(20) Thus, previous experiences should be considered as they can in uence knowledge and screening aptitudes.(21) Another important nding of our study was that knowledge of HPV infection was low among participants who perceived having poor or regular health as compared to the study of Gillis et.al.(22) where selfperceived risk in uenced HPV-related knowledge.This suggests that the perception of poor health could become a barrier to the interest in obtaining more knowledge about HPV.
Equally important, although 40.3% had adequate knowledge of HPV infection and 53.8% of participants were aware of HPV vaccination, only 7.5% of participants were vaccinated.Contrary, in the study of Amboree et al. they reported that PLWH had lower knowledge of HPV besides a higher vaccine uptake.(23) They assume that this could be related to their engagement to care.Meanwhile, in studies of women (24) and men (25) living with HIV in Canada, a lower HPV vaccine uptake was reported while they demonstrated engagement with regular care.(25) On the other hand, limited knowledge about AC risk-factors was reported by the participants of this study.This is similar to the studies of Rodriguez et al. and Wells et al., that show a lack of awareness and knowledge about AC risk in women living with HIV and HIV-negative women living in the US.(9, 18) Also, other studies among gay and bisexual men and young men living in the US reported a lack of information about AC. (19,23) Contrariwise, participants with more than 15 years of having the diagnosis of HIV, demonstrate more knowledge about AC risk-factors presenting the possibility that PLWH are more expose to health education and medical resources, leading to more awareness or their experiences stimulated them to become informed about potential complications like AC.
Study ndings suggest a challenge for primary care professionals because health illiteracy has been identi ed as a main barrier to cancer prevention, affecting the engagement of PLWH with preventive activities.(26)Innovative preventive methods are needed for early detection and the improvement of AC management.(27) These efforts should also include the importance of HPV vaccination, since although the majority of subjects were aware of HPV vaccination, less than 10% were vaccinated.Primary care professionals are considered a thrust source of information (26) thus there is a big responsibility to train this population with the latest information about HPV infection, AC risk-factors and prevention strategies.

STUDY STRENGTH AND LIMITATIONS
Our study is one of the few to evaluate HPV awareness and knowledge and AC risk-factors knowledge among a Hispanics living with HIV.Results underscore the need for increased awareness and knowledge about HPV and AC among high-risk populations.Limitations include self-reported nature of the data, which could lead to information bias, and the use of a convenience sample, limiting the generalizability of the ndings to all PLWH in Puerto Rico.

CONCLUSIONS
Despite high awareness of HPV, limited knowledge about HPV and AC risk factors were observed among this Hispanic population of PLWH living in PR, underscoring the need for educational efforts within this population as an AC prevention strategy.Although PLWH are at a higher risk of developing AC, our study revealed that few individuals have adequate knowledge of AC; despite that more than half of the participants were up to date with AC screening recommendations (having undergone anal Pap test during the last 12 months).Additionally, despite awareness of the HPV vaccine, less than 10% were vaccinated against it.Educational efforts should focus on the importance of AC screening and HPV vaccination, as well as on the risk-factors for cancer, particularly among PLWH.

Table 5 :
Logistic regression models of factors associated to HPV infection awareness strati ed by age.